The long-term objectives of this project include the characterization of biochemical differences between a specific subset of T-lymphocytes from normal and systemic lupus erythematosus (SLE) patients. The subset is enriched in T-helper cells and has the phenotype RFcGamma-, T3+, T4+. Previous work has shown that this subset can undergo partial conversion to T-suppressor cells in response to adenosine with expression of RFCGamma and T3. The response to adenosine is lacking in T-cells prepared from SLE patients. Moreover, normal T-cells respond to adenosine with increased cAMP levels, while while SLE T-cells show decreased cAMP levels in response to adenosine. It is therefore proposed to comparatively study adenosine receptors and the biochemical events distal to their occupancy in both normal and SLE T-cells to determine the reason for the defective response to adenosine in the SLE cells. Adenosine receptors will be studied with radiolabeled adenosine analogues and with the photoaffinity probe [3H]-8-azidoadenosine. The absence or presence of Ri, Ra, and P-site adenosine receptors will be determined. cAMP levels will be measured in response to cholera exterotoxin and forskolin to test for the G/F subunit and the catalyic subunit of hormone-sensitive adenylate cyclase. cAMP binding proteins will be studied using the photoaffinity probe [32P]-8-azido-cAMP to determine whether the SLE T-cel defect might lie at the level of the cAMP-dependent protein kinase. Protein phosphorylation in intact T-cells will be studied in response to adenosine and other pharmacologic agents to characterize specific events that may mediate the immunosuppressor response to adenosine and that may be defective in SLE cells. By these methods, it is hoped to describe some of the underlying cellular and biochemical defects that may account for abnormal immunosuppression in SLE.